Keloids and Hypertrophic Scars

Keloids and hypertrophic scars are types of abnormal (pathological) scarring in which the skin produces too much collagen — the structural protein that gives skin its strength — during the wound-healing process. Instead of forming a flat, fading scar, the skin creates a raised, thickened, often firm mass of scar tissue.

The key difference between the two:

• Hypertrophic scars stay within the boundaries of the original wound. They are raised and firm but tend to improve on their own over months to years
• Keloids grow beyond the edges of the original wound, invading surrounding normal skin. They do not regress spontaneously and may continue to enlarge over time

Both can develop after any form of skin injury — surgery, burns, acne, piercings, vaccinations, or even minor scratches — though keloids can occasionally appear without a clear triggering injury.

Keloids and hypertrophic scars can affect anyone, but certain groups are at considerably higher risk.

• Prevalence: Hypertrophic scars develop in up to 70% of burn patients and after 40–70% of surgical procedures. Keloids affect an estimated 6–16% of people of African descent
• Ethnicity: People with darker skin (Fitzpatrick skin types IV–VI) — particularly those of African, Asian, and Hispanic ancestry — are significantly more prone to keloid formation
• Age: Most common between 10 and 30 years of age; rare in the very young and elderly
• Family history: A strong genetic component exists — having a first-degree relative with keloids substantially increases your risk
• Body sites: Certain areas are particularly prone: earlobes, shoulders, upper chest (sternum), upper back, and the jawline. Conversely, the eyelids, palms, soles, and genitalia are rarely affected
• Triggers: Ear piercings, acne, surgical incisions, burns, and vaccinations are among the most common causes. Even minor injuries can trigger keloids in susceptible individuals

The appearance and symptoms differ between the two types.

Hypertrophic scars:

• Raised, firm, often red or pink scar that stays within the wound boundaries
• Usually develops within weeks of the injury
• May feel tight or restrictive, especially over joints (scar contracture)
• Tends to flatten and soften gradually over 1–2 years
• Itching is common, particularly during the maturation phase

Keloids:

• Firm, rubbery, shiny nodule or plaque that extends beyond the original wound margins
• Colour varies: pink, red, or dark brown/purple, often darker than the surrounding skin
• May develop months or even years after the initial injury
• Does not regress spontaneously — may continue to grow slowly over years
• Frequently itchy, painful, or tender; some patients describe a burning or stinging sensation
• Surface may be smooth or irregular; claw-like projections can develop at the edges
• Can be cosmetically disfiguring and functionally limiting (restriction of movement near joints)

Psychosocial impact: Keloids and hypertrophic scars — particularly those on visible areas such as the face, neck, or chest — can cause significant emotional distress. Patients commonly report embarrassment, reduced self-confidence, anxiety about their appearance, and avoidance of social situations. This psychological burden should not be underestimated.

The exact mechanism is not fully understood, but the central problem is a prolonged and excessive inflammatory response in the deep layer of the skin (reticular dermis) during wound healing.

• Excessive collagen production: Fibroblasts (the cells responsible for producing collagen) become overactive, producing dense, disorganized collagen fibres rather than the orderly, parallel arrangement found in normal scars
• Chronic inflammation: Pro-inflammatory signals — particularly TGF-β (transforming growth factor beta) — remain elevated far longer than in normal wound healing, driving continuous fibroblast activation
• Genetic predisposition: Multiple gene variants have been identified; the condition runs strongly in families, with autosomal dominant inheritance patterns in some. People of African and Asian ancestry carry higher genetic susceptibility
• Mechanical tension: Scars over areas of high skin tension (chest, shoulders, joints) are more prone to pathological scarring. Mechanical forces stimulate fibroblast activity through mechanotransduction pathways
• Melanin: Recent research suggests that increased melanin production may promote fibroblast proliferation, which may partly explain the higher incidence in darker-skinned individuals

Diagnosis is clinical — based on the appearance and history of the scar.

• Clinical examination: A firm, raised scar that extends beyond the wound margins (keloid) or stays within them (hypertrophic scar). Location, time course, and relationship to the original wound are key diagnostic features
• Patient history: Previous scarring behaviour, family history, and triggering injury. It is important to ask about a history of keloid formation before any elective surgery or piercing
• Skin biopsy: Not routinely needed but may be performed to exclude other conditions. Histology shows thick, hyalinized (glassy) collagen bundles arranged haphazardly in keloids, compared to the parallel arrangement seen in hypertrophic scars
• Differential diagnosis: Dermatofibroma, dermatofibrosarcoma protuberans (DFSP), lobomycosis, and morphea (localized scleroderma) may occasionally resemble keloid scars and should be considered if the presentation is atypical

There is no single cure for keloids, and recurrence after treatment is common. The most effective approach combines multiple treatments (multimodal therapy). Hypertrophic scars have a better prognosis and often improve with conservative measures alone.

Prevention (the most effective strategy):

• Avoid unnecessary surgery, piercings, or tattoos if you are prone to keloids
• If surgery is needed, inform your surgeon about your scarring history so that preventive measures can be used
• Silicone gel sheets or silicone gel applied to fresh wounds can help prevent abnormal scarring
• Tension-reducing wound closure techniques and careful postoperative care reduce risk

First-line treatment:

• Silicone gel sheets or gel: The gold standard for non-invasive treatment and prevention. Worn over the scar for at least 12 hours per day for 3–6 months. Evidence-based, safe, and well tolerated
• Intralesional corticosteroid injections: Triamcinolone acetonide (10–40 mg/mL) injected directly into the scar every 4–6 weeks. The most commonly used active treatment — can flatten keloids and relieve itching and pain. Side effects include skin thinning (atrophy), depigmentation, and telangiectasias at the injection site

Second-line and combination treatments:

• Intralesional 5-fluorouracil (5-FU): Often combined with corticosteroids for improved results and fewer side effects. Effective for flattening and softening resistant scars
• Cryotherapy: Freezing the scar tissue — can be effective for small keloids; may cause depigmentation
• Laser therapy: Pulsed dye laser (PDL) can reduce redness and improve texture; fractional CO₂ laser may enhance drug delivery. Evidence remains limited but promising
• Pressure therapy: Compression garments or pressure earrings, especially useful for ear keloids and burns-related hypertrophic scars. Must be worn consistently for many months
• Surgical excision: Removing the keloid surgically — but excision alone has a recurrence rate of 45–100%. Always combined with adjuvant therapy (corticosteroid injections, radiation, or 5-FU) to reduce recurrence
• Radiotherapy: Post-excision superficial radiotherapy or brachytherapy significantly reduces recurrence. Reserved for severe, recurrent keloids that have failed other treatments

Emerging treatments: Botulinum toxin A (injected into the scar to reduce tension and symptoms), intralesional verapamil, and biologic therapies targeting specific inflammatory pathways are under investigation. These are not yet standard treatments.

• Keloids and hypertrophic scars are not dangerous — they are benign, but they can cause significant discomfort and affect quality of life
• Prevention is key: If you know you scar easily or have a family history of keloids, avoid unnecessary skin procedures (piercings, tattoos, elective surgery) whenever possible
• There is no guaranteed cure for keloids — even the best treatments carry a risk of recurrence. Setting realistic expectations is important
• A multimodal approach (combining treatments) is consistently more effective than any single treatment
• Silicone products (sheets or gel) are safe, effective, and should be started early on any wound in a keloid-prone individual
• When to seek medical attention: Any scar that continues to grow, becomes painful or intensely itchy, restricts movement, or causes emotional distress should be evaluated by a dermatologist. Seek prompt attention if a firm lump appears within a scar that looks different from the rest — rarely, other skin conditions can mimic keloids
• Treatment takes time — many therapies require weeks to months of consistent use before results become apparent. Patience and adherence are essential
• The psychological impact of keloids is real and valid — do not hesitate to discuss your concerns with your doctor, and consider psychological support if scarring significantly affects your wellbeing

• Global burden: Pathological scarring (keloids and hypertrophic scars) affects hundreds of millions of patients worldwide (Jeschke et al., 2023)
• Incidence: Hypertrophic scars develop in up to 70% of burn injuries and 40–70% of surgical procedures, depending on wound location, closure technique, and patient factors
• Keloid prevalence by ethnicity: 6–16% in populations of African descent; 0.09% in Caucasian populations (UK data). Higher prevalence also reported in Asian and Hispanic populations
• Age distribution: Peak incidence 10–30 years; rare before age 2 and after age 65. Hormonally influenced — worsening during puberty and pregnancy reported
• Gender: Historically reported as more common in females, but this likely reflects higher rates of ear piercing and cosmetic procedures; intrinsic gender susceptibility appears equal (Berman et al., 2017)
• Anatomical predilection: Anterior chest (sternum), deltoid, upper back, earlobes, jawline. Sites of high skin tension are most vulnerable. Eyelids, genitalia, palms, and soles are conspicuously spared
• Familial clustering: 5–10 fold increased risk with affected first-degree relatives. Both autosomal dominant (with incomplete penetrance) and autosomal recessive patterns described
• Genetic associations: GWAS studies have identified susceptibility loci at 1q41, 3q22.3–23, 15q21.3, and 18q21.1. HLA-DRB1*15 association in Chinese populations. NEDD4 gene variants associated with keloid formation in Japanese studies

Normal wound healing

Wound healing proceeds through four overlapping phases: haemostasis, inflammation, proliferation, and remodelling. In normal healing, inflammation resolves, fibroblasts deposit organized type III collagen (later replaced by type I), and the scar gradually matures and softens over 6–18 months.

Pathological scarring: the fibrotic phenotype

In keloids and hypertrophic scars, this process derails at the inflammation–proliferation transition. Key mechanisms:

Chronic reticular dermis inflammation (Ogawa, 2017):

• Superficial injuries that do not reach the reticular dermis never cause pathological scarring — this observation is foundational
• Pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α) remain persistently elevated in keloid tissue
• The clinical differences between keloids and hypertrophic scars reflect differences in the intensity, frequency, and duration of reticular dermis inflammation — they are on a spectrum, not distinct entities

TGF-β/Smad signalling — the central fibrotic pathway:

• TGF-β1 is overexpressed in keloid fibroblasts, driving fibroblast-to-myofibroblast differentiation
• Sustained activation of Smad2/3 (pro-fibrotic) with reduced Smad7 (anti-fibrotic inhibitor)
• Downstream: excessive synthesis of type I and III collagen, fibronectin, and proteoglycans
• Additional pathways: PI3K/AKT/mTOR, Wnt/β-catenin, Notch, JAK/STAT all contribute to the fibrotic phenotype

Immune dysregulation:

• M2 macrophage polarization predominates → pro-fibrotic cytokine milieu (IL-4, IL-10, IL-13, TGF-β)
• Th2/Th17 bias: IL-17 amplifies inflammation via IL-6 and activates TGF-β/Smad (Bitterman et al., 2024)
• Regulatory T cells (Tregs) secrete TGF-β and IL-10, paradoxically promoting fibrosis while suppressing anti-fibrotic cytotoxic immune responses
• Dysfunctional CD8+ T cells and NK cells → impaired elimination of overactive fibroblasts (Wu et al., 2026)

Mechanotransduction:

• Mechanical tension is one of the initiating factors in keloid formation (Feng et al., 2022)
• Increased matrix stiffness activates fibroblast fibrotic phenotype via integrin–FAK, YAP/TAZ, and calcium ion pathways, creating a positive feedback loop
• Explains the anatomical predilection for areas of high skin tension (sternum, shoulders, deltoid)

Melanin and ferroptosis resistance (Shi et al., 2025):

• Novel finding: melanocyte-secreted melanin promotes fibroblast proliferation, migration, and collagen synthesis through iron overload and ferroptosis resistance
• Melanin levels correlate positively with keloid severity (KASI score)
• May partially explain the higher incidence in darker-skinned individuals
• MITF inhibitor ML329 suppresses keloid formation in animal models — potential new therapeutic target

Collagen architecture:

• Keloids: thick, hyalinized collagen bundles in a haphazard, whorl-like pattern; type I/III ratio elevated
• Hypertrophic scars: collagen bundles parallel to the epidermis in a nodular arrangement; more organized than keloid but less so than mature scar
• Keloid collagen extends into the deep dermis and subcutaneous tissue; hypertrophic scar collagen is confined to the papillary and upper reticular dermis

Hypertrophic scars

• Raised, erythematous, firm scar confined to the wound boundaries
• Onset: weeks to months after injury
• Growth pattern: rapid initial growth, then stabilization and spontaneous regression over 1–2 years in most cases
• Symptoms: pruritus (especially during active growth), tightness, scar contracture over joints
• Association: particularly common after burn injuries, surgical incisions perpendicular to relaxed skin tension lines (RSTLs), and wounds healing by secondary intention
• Histology: organized, parallel collagen bundles with nodular arrangement; α-SMA-positive myofibroblasts; blood vessels oriented parallel to the epidermis

Keloids

• Firm, rubbery, shiny nodule or plaque extending beyond the wound boundaries
• Onset: months to years after injury; can appear without identifiable trauma
• Growth pattern: continuous slow growth; no spontaneous regression
• Colour: red, pink, dark brown, or violaceous; often hyperpigmented
• Symptoms: pruritus (54–86%), pain/tenderness (22–46%), burning sensation
• Morphology: can develop pedunculated or claw-like projections; butterfly (dumbbell) keloids on earlobes after piercing
• Predilection: earlobes (after piercing), sternum, deltoid, upper back, jawline
• Histology: thick, hyalinized, eosinophilic collagen bundles in a haphazard whorl-like arrangement (keloid-type collagen); prominent mucin deposits; sparse fibroblasts between thick collagen; often a tongue-like advancing margin
• Hallmark: extends beyond the papillary dermis deep into the reticular dermis and sometimes subcutaneous fat

Assessment tools

• Vancouver Scar Scale (VSS): Assesses pigmentation, vascularity, pliability, and height (0–13 score). Most widely used in clinical trials
• Patient and Observer Scar Assessment Scale (POSAS): Includes both patient-reported and observer-reported components — superior for capturing subjective symptoms
• Japan Scar Workshop Scar Scale (JSS): Objective scoring of risk factors for pathological scarring — facilitates treatment planning
• Keloid Area and Severity Index (KASI): Quantitative assessment of keloid burden

Diagnostic criteria

No consensus formal criteria exist. Diagnosis is clinical:

• Keloid: scar tissue extending beyond the margins of the original wound, not regressing spontaneously
• Hypertrophic scar: raised scar confined to the original wound boundaries, with tendency toward spontaneous regression

The Japan Scar Workshop (JSW) diagnostic flowchart (Ogawa et al., 2019) provides a structured approach: wound history → scar assessment → classification as mature scar, hypertrophic scar, keloid, or keloid-hypertrophic scar overlap.

Not routinely required. Indications: atypical clinical presentation, suspicion of malignancy, or failure to respond to treatment.

• Keloid: thick, hyalinized, deeply eosinophilic collagen bundles in a random arrangement (the pathognomonic "keloid collagen"); α-SMA-positive myofibroblasts less prominent than in HTS; often tongue-like advancing edge; mucin deposits; mast cell infiltration
• Hypertrophic scar: parallel collagen bundles with nodular architecture; prominent α-SMA-positive myofibroblasts; flattened epidermis; vertical blood vessels

Condition	Key distinguishing features
Dermatofibroma	Small, firm papule/nodule; dimple sign on lateral compression; no wound history
Dermatofibrosarcoma protuberans (DFSP)	Slow-growing, firm plaque; locally aggressive; CD34+ on immunohistochemistry
Lobomycosis (lacaziosis)	Keloid-like nodules; endemic to Amazon basin; Lacazia loboi on histology
Morphea (localized scleroderma)	Sclerotic plaques; no clear wound history; "lilac ring" border
Foreign body granuloma	History of implanted material; multinucleated giant cells on biopsy
Scar sarcoidosis	Granulomatous infiltration of scars; non-caseating granulomas on histology

Prevention

Prevention is the most effective strategy — treatment of established keloids is difficult and recurrence is high.

• Risk assessment: Identify keloid-prone individuals before any elective procedure (personal and family history, ethnicity, body site)
• Surgical technique: Tension-free closure along RSTLs; avoidance of midline incisions where possible; subcuticular/absorbable sutures; minimize tissue trauma
• Silicone prophylaxis: Silicone gel sheets or topical silicone gel applied to healing wounds starting 2 weeks post-surgery and continued for ≥3 months. Recommended by international consensus guidelines as first-line prevention (Monstrey et al., 2014; Gold et al., 2014)
• Tension offloading: Paper tape, tension-reducing devices (Embrace), or steri-strips across the wound for 8–12 weeks post-closure
• Avoidance: Advise keloid-prone patients to avoid elective piercings, tattoos, and unnecessary surgical procedures

Pharmacological treatment

First-line: intralesional corticosteroids

• Triamcinolone acetonide (TAC) 10–40 mg/mL intralesional injection
• Mechanism: inhibits fibroblast proliferation, collagen synthesis, and TGF-β expression; promotes collagen degradation via metalloproteinase induction
• Protocol: inject into the scar body (not beneath it) using a 26–30 gauge needle or luer-lock syringe with firm pressure; inject until blanching of scar tissue
• Interval: every 4–6 weeks, typically 3–6 sessions
• Efficacy: 50–100% regression reported; 33% recurrence at 1 year, 50% at 5 years (Morelli Coppola et al., 2018)
• Adverse effects: atrophy, depigmentation (especially Fitzpatrick V–VI), telangiectasia, pain during injection
• Maximum dose per session: 20–80 mg depending on scar size

Second-line: intralesional 5-fluorouracil (5-FU)

• 50 mg/mL, often combined with TAC (TAC 40 mg/mL : 5-FU 50 mg/mL in 1:9 ratio) ± triamcinolone to reduce side effects
• Mechanism: inhibits fibroblast proliferation by blocking thymidylate synthase
• Efficacy: flattening and softening of resistant scars; one study showed no recurrence at 2 years after excision + 5-FU (LaRanger et al., 2019)
• Triple combination (TAC + 5-FU + hyaluronidase) showed superior results to TAC alone in height, pliability, and modified VSS (Ehsani et al., 2025)
• Adverse effects: pain, purpura, superficial ulceration (less common than with TAC alone)

Adjunctive: botulinum toxin A

• Intralesional injection reduces muscle tension across the scar and modulates TGF-β expression
• Meta-analyses show superiority to corticosteroid alone for VAS pain and VSS improvement (Bi et al., 2019; Liu et al., 2021)
• Particularly useful for keloids in areas of high muscular tension
• Evidence level: promising but not yet established as standard monotherapy

Non-pharmacological treatment

Silicone products

• Mechanism: occlusion and hydration of the stratum corneum; reduction of TEWL; modulation of fibroblast cytokine production
• Products: silicone gel sheets (most evidence), topical silicone gel (more practical for irregular areas)
• Protocol: minimum 12 hours/day for 3–6 months; start as soon as wound is epithelialized
• Evidence: recommended as first-line by all major international guidelines (Gold et al., 2014; Monstrey et al., 2014)

Compression therapy

• 24–30 mmHg sustained pressure for ≥23 hours/day for 6–12 months
• Most effective for earlobe keloids (custom pressure earrings) and post-burn hypertrophic scars
• Mechanism: induces local tissue hypoxia → fibroblast apoptosis and collagen remodelling

Cryotherapy

• Intralesional cryotherapy (CryoShape device) or surface spray cryotherapy
• Mechanism: direct cellular damage, microvascular occlusion
• Most effective for small keloids; may cause hypopigmentation (limiting utility in darker skin types)
• One RCT found intralesional cryotherapy inferior to excision + brachytherapy (Bijlard et al., 2018)

Laser therapy

• Pulsed dye laser (PDL, 585/595 nm): reduces erythema and vascularity; may improve scar texture. Cochrane review found low-certainty evidence of benefit (Leszczynski et al., 2022)
• Fractional CO₂ laser: creates microchannels for laser-assisted drug delivery (LADD) of TAC or 5-FU; comparable results to intralesional TAC in one RCT (Tawaranurak et al., 2022)
• Nd:YAG (1064 nm): 65% scar reduction on VSS in some studies (Jackson et al., 2025)

Surgical excision + adjuvant therapy

• Excision alone: recurrence rate 45–100% — never recommended as monotherapy for keloids
• Core excision (intramarginal): removes keloid bulk while preserving rim to minimize wound tension and recurrence
• Post-excision adjuvant (essential):
  • Intralesional TAC ± 5-FU: started within 24–48 hours, continued monthly for 6–12 months
  • Radiotherapy: superficial X-ray (SXR), electron beam, or brachytherapy within 24 hours of excision. Significantly reduces recurrence. Generally reserved for severe, recurrent keloids
  • Brachytherapy (interstitial or superficial): comparable or superior to external beam for keloid recurrence prevention (Goutos & Ogawa, 2017)
• Radiation carcinogenesis risk: theoretical concern but no documented cases of radiation-induced malignancy from keloid radiation in published literature. Risk considered extremely low with modern techniques

Treatment algorithm (adapted from Ogawa, 2022; Abbadi et al., 2026)

Layer 1 — Prevention and mild scars: Silicone gel/sheets + sun protection + tension offloading

Layer 2 — Established keloids/HTS: Intralesional TAC (± 5-FU) as pharmacological backbone. Add adjuncts based on clinical features:

• Thin/flat lesions → cryotherapy
• Thick/textured lesions → fractional CO₂ laser ± LADD
• Tension-related/pruritic → botulinum toxin A
• Contracture (HTS) → physical therapy + silicone + possible Z-plasty

Layer 3 — Severe or recurrent keloids: Surgical excision + immediate adjuvant radiotherapy (SXR or brachytherapy) + continued intralesional injections. Long-term follow-up (minimum 2 years) is critical — late recurrence is common.

Monitoring

• Follow-up at 4–6 week intervals during active treatment
• Assess scar volume, symptoms (itch, pain), and functional impact at each visit
• Post-treatment surveillance for minimum 2 years (recurrence can be late)
• Standardized assessment tools (VSS, POSAS) recommended for tracking response
• Watch for corticosteroid adverse effects: atrophy, depigmentation, telangiectasia

Pediatric considerations

• Keloids can develop as early as age 2 but are uncommon before puberty
• Ear piercing is a common trigger in children and adolescents — counsel families with a positive keloid history
• Treatment approach is similar to adults; silicone products are first-line
• Intralesional TAC is effective and safe in children at reduced concentrations (5–10 mg/mL)
• Radiotherapy is generally avoided in children due to theoretical long-term risks

Pregnancy

• Keloids may enlarge during pregnancy (hormonal influence)
• Silicone products are safe during pregnancy
• Intralesional TAC: limited safety data; generally deferred until postpartum
• Surgical procedures and radiotherapy contraindicated during pregnancy

Darker skin types (Fitzpatrick IV–VI)

• Higher intrinsic susceptibility to keloid formation
• Depigmentation from TAC injections or cryotherapy is a significant concern — use lower concentrations and short treatment cycles
• Melanin-mediated fibroblast activation may contribute to pathogenesis (Shi et al., 2025)
• Culturally sensitive counselling about prevention (piercings, tattoos, traditional scarification practices)

• Hypertrophic scars: Generally favourable. Most flatten and soften over 1–2 years. Treatment accelerates this process and reduces contracture
• Keloids: Chronic condition with high recurrence rates. Even with optimal multimodal therapy, recurrence rates range from 10–50% depending on body site, scar size, and treatment modality
• Earlobe keloids: Best prognosis — excision + adjuvant therapy achieves cure rates of 70–90%
• Trunk/sternum keloids: Worst prognosis — recurrence rates remain high even with aggressive multimodal treatment
• Quality of life: Both conditions significantly impact quality of life through pain, pruritus, cosmetic disfigurement, and psychosocial distress. The DLQI (Dermatology Life Quality Index) is elevated in keloid patients, comparable to moderate psoriasis or atopic dermatitis

Primary prevention

• Patient education: identify and counsel keloid-prone individuals before elective procedures
• Avoidance: defer non-essential piercings, tattoos, and cosmetic procedures in high-risk patients
• Wound care: minimize wound tension, avoid wound infection, remove sutures early

Secondary prevention (early intervention)

• Silicone gel/sheets applied to all surgical wounds in keloid-prone patients starting at epithelialization
• Tension-reducing wound closure (subcuticular sutures, paper taping for 8–12 weeks)
• Pressure garments for burn patients beginning as soon as wounds heal (23 hours/day for ≥6 months)

Tertiary prevention (recurrence prevention)

• Multimodal adjuvant therapy after excision: intralesional TAC ± 5-FU ± radiotherapy
• Long-term follow-up with reassessment at 6, 12, and 24 months post-treatment
• Patient education on wound care and early intervention for new injuries

• Melanin–ferroptosis axis: Melanocyte-secreted melanin promotes keloid fibroblast activity via iron overload; MITF inhibitors show preclinical promise (Shi et al., 2025)
• Biologic therapies: Dupilumab (IL-4/IL-13 inhibitor) has shown variable responses in early case reports (Grade D evidence); anti-TGF-β (fresolimumab, AVID200), anti-IL-6 (tocilizumab), and anti-TSLP (tezepelumab) are under investigation (Chen et al., 2026)
• Precision immunotherapy: Targeting the Th2/Th17 imbalance and restoring cytotoxic immune surveillance against overactive fibroblasts
• Laser-assisted drug delivery (LADD): Fractional CO₂ laser creates microchannels for enhanced penetration of TAC, 5-FU, or other agents
• Intralesional insulin: One study showed 66.6% volume reduction, comparable to corticosteroids, with fewer side effects — potential alternative (Elradi et al., 2025)
• Layered treatment algorithms: The 2026 layered management approach (Abbadi et al.) provides a pragmatic, stepwise framework with modality selection based on clinical features

• "If it's beyond the wound margins, it's a keloid. If it's within, it's hypertrophic." — the single most reliable clinical distinction
• Ask about scarring history before any procedure — preventing a keloid is far easier than treating one
• Excision alone for keloids = guaranteed recurrence. Always combine with adjuvant therapy
• TAC + 5-FU is more effective and causes fewer side effects than TAC alone — consider it as first-line combination
• Earlobe keloids have the best prognosis; sternal keloids the worst. Counsel patients accordingly
• Scar maturation takes 12–24 months — early hypertrophic scars should be given time and conservative treatment before considering aggressive intervention
• Depigmentation from TAC is cosmetically significant in skin of colour — use lower concentrations (10 mg/mL) and fewer cycles
• Long-term follow-up (≥2 years) is non-negotiable — late recurrence is the rule, not the exception